Variant 6-43132496-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002821.5(PTK7):c.1037C>G(p.Pro346Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,610,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

PTK7
NM_002821.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

PTK7 (HGNC:9618): (protein tyrosine kinase 7 (inactive)) This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

PTK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.813

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK7	NM_002821.5 linkuse as main transcript	c.1037C>G	p.Pro346Arg	missense_variant	7/20	ENST00000230419.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK7	ENST00000230419.9 linkuse as main transcript	c.1037C>G	p.Pro346Arg	missense_variant	7/20	1	NM_002821.5	P1	Q13308-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250374

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000892

AC:

AN:

1458090

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.1037C>G (p.P346R) alteration is located in exon 7 (coding exon 7) of the PTK7 gene. This alteration results from a C to G substitution at nucleotide position 1037, causing the proline (P) at amino acid position 346 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;.;.;.;.;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.81

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.019

MutationAssessor

Uncertain

2.4

M;.;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;N

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.8

D;D;D;D;D;D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.0040

D;D;D;D;T;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;.;.

Vest4

0.91

MutPred

0.58

Loss of catalytic residue at P345 (P = 0.016);Loss of catalytic residue at P345 (P = 0.016);Loss of catalytic residue at P345 (P = 0.016);Loss of catalytic residue at P345 (P = 0.016);Loss of catalytic residue at P345 (P = 0.016);.;.;

MVP

0.73

MPC

1.2

ClinPred

0.99

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over